Sachin J. Shah, MD, MPH; Mark H. Eckman, MD; Sara Aspberg, MD, PhD; Alan S. Go, MD; Daniel E. Singer, MD
Disclaimer: Dr. Shah had full access to all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.
Financial Support: Dr. Eckman has current or recent investigator-initiated grant funding from the Heart Rhythm Society (through a grant from Boehinger Ingelheim), the National Center for Advancing Translational Sciences (NIH – UL1TR000077-05), Pfizer Educational Group, Bristol-Myers Squibb–Pfizer Education Consortium, and the Cystic Fibrosis Foundation. Dr. Go has a research grant through Kaiser Permanente Northern California Division of Research from iRhythm Technologies. Dr. Singer is supported, in part, by the Eliot B. and Edith C. Shoolman Fund of Massachusetts General Hospital. He receives research support from Bristol-Myers Squibb and Boehringer Ingelheim.
Disclosures: Dr. Eckman has current or recent investigator-initiated grant funding from the Heart Rhythm Society (through a grant from Boehringer Ingelheim), the National Center for Advancing Translational Sciences, Pfizer Educational Group, Bristol-Myers Squibb–Pfizer Education Consortium, and the Cystic Fibrosis Foundation outside the submitted work. Dr. Go reports grants from iRhythm Technologies during the conduct of the study. Dr. Singer reports grants and personal fees from Boehringer Ingelheim and Bristol-Myers Squibb and personal fees from Johnson & Johnson, CVS Health, Medtronic, Merck, and Pfizer outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2762.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Readers with questions about the simulation model used in this analysis may contact Dr. Shah (e-mail, firstname.lastname@example.org). The model is not available without a written agreement with the authors.
Corresponding Author: Sachin J. Shah, MD, MPH, Division of Hospital Medicine, 533 Parnassus Avenue, U130, San Francisco, CA 94143; e-mail, email@example.com.
Current Author Addresses: Dr. Shah: Division of Hospital Medicine, 533 Parnassus Avenue, U130, San Francisco, CA 94143.
Dr. Eckman: University of Cincinnati, Division of General Internal Medicine, 231 Albert Sabin Way, Box 0535, Cincinnati, OH 45267-0535.
Dr. Aspberg: Department of Cardiology, Danderyd Hospital, S-182 88, Stockholm, Sweden.
Dr. Go: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612-2304.
Dr. Singer: Division of General Internal Medicine, 100 Cambridge Street, 16th Floor, Massachusetts General Hospital, Boston, MA 02114.
Author Contributions: Conception and design: S.J. Shah, M.H. Eckman, D.E. Singer.
Analysis and interpretation of the data: S.J. Shah, M.H. Eckman, A.S. Go, D.E. Singer.
Drafting of the article: S.J. Shah, M.H. Eckman, D.E. Singer.
Critical revision of the article for important intellectual content: S.J. Shah, M.H. Eckman, S. Aspberg, A.S. Go, D.E. Singer.
Final approval of the article: S.J. Shah, M.H. Eckman, S. Aspberg, A.S. Go, D.E. Singer.
Provision of study materials or patients: M.H. Eckman, A.S. Go, D.E. Singer.
Statistical expertise: S.J. Shah, M.H. Eckman, D.E. Singer.
Administrative, technical, or logistic support: M.H. Eckman, S. Aspberg, A.S. Go, D.E. Singer.
Collection and assembly of data: S.J. Shah, A.S. Go, D.E. Singer.
Stroke rates in patients with nonvalvular atrial fibrillation (AF) who are not receiving anticoagulant therapy vary widely across published studies; the resulting effect on the net clinical benefit of anticoagulation in AF is unknown.
To determine the effect of variation in published AF stroke rates on the net clinical benefit of anticoagulation.
Markov model decision analysis. Warfarin was the base case, and non–vitamin K antagonist oral anticoagulants (NOACs) were modeled in a secondary analysis.
33 434 adults with incident AF.
Quality-adjusted life-years (QALYs).
Of the 33 434 patients, 27 179 had a CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score of 2 or more. The population benefit of warfarin anticoagulation for these patients was least using stroke rates from the ATRIA (AnTicoagulation and Risk Factors In Atrial Fibrillation) study and greatest using those from the Danish National Patient Registry (6290 QALYs [95% CI, ±2.3%] vs. 24 110 QALYs [CI, ±1.9%]; P < 0.001). The optimal CHA2DS2-VASc score threshold for anticoagulation was 3 or more using stroke rates from ATRIA, 2 or more using those from the Swedish AF cohort study, 1 or more using those from the SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) study, and 0 or more using those from the Danish National Patient Registry. Accounting for lower rates of NOAC-associated intracranial hemorrhage decreased optimal CHA2DS2-VASc score thresholds, but these thresholds still varied widely.
Measured benefit may not generalize to other populations.
Variation in published AF stroke rates for patients not receiving anticoagulant therapy results in multifold variation in the net clinical benefit of anticoagulation. Guidelines should better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation.
Shah SJ, Eckman MH, Aspberg S, et al. Effect of Variation in Published Stroke Rates on the Net Clinical Benefit of Anticoagulation for Atrial Fibrillation. Ann Intern Med. 2018;169:517–527. [Epub ahead of print 25 September 2018]. doi: https://doi.org/10.7326/M17-2762
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Published: Ann Intern Med. 2018;169(8):517-527.
Published at www.annals.org on 25 September 2018
Cardiology, Neurology, Rhythm Disorders and Devices, Stroke.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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